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A second messenger required for nerve growth factor biological activity?

Abstract

After binding to specific membrane receptors of target neurones and responsive phaeochromocytoma cells, nerve growth factor (NGF) is internalized and accumulated in the perikaryon within membrane-confined compartments (H. Rohrer et al., unpublished observation, and refs 1–5). Although quantitative electron microscopic autoradiography and ultrahistochemical studies gave no evidence for further movement of NGF1,2,4,5, it was claimed on the basis of light microscopy of PC12 cells (ref. 6 and P.C. Marchisio, personal communication) that some of the NGF taken up by the cell reaches the free cytoplasm and subsequently the nucleus where it would exert a physiological effect. We report here that the direct introduction of NGF into the free cytoplasm of phaeochromocytoma cells by fusion with NGF-loaded erythrocyte ghosts does not induce fibre outgrowth, in contrast to the normal response of these cells seen when NGF is added to the culture medium. Correspondingly, NGF antibodies introduced into the cytoplasm do not prevent fibre outgrowth evoked by NGF added to the culture medium. Thus, the binding of NGF to its receptor must result in the production of a second messenger either from the cell surface or after internalization from an intracellular compartment7,8.

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Heumann, R., Schwab, M. & Thoenen, H. A second messenger required for nerve growth factor biological activity?. Nature 292, 838–340 (1981). https://doi.org/10.1038/292838a0

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